• Pharmacology · Jan 1994

    Sodium ions modulate differentially the effect of a benzodiazepine agonist on rat spinal mu-, delta- and kappa-opioid receptors.

    • A K Rattan and G A Tejwani.
    • Department of Pharmacology and Anesthesiology, Ohio State University College of Medicine, Columbus.
    • Pharmacology. 1994 Jan 1;48(1):30-40.

    AbstractMidazolam, a benzodiazepine receptor agonist, when injected intrathecally either enhances or decreases antinociception produced by intrathecal administration of morphine in rats. Furthermore, midazolam inhibits binding of several opioid ligands to spinal opioid receptors in vitro [Rattan et al, Anesth Analg 1991;73:124-131]. This study was designed to investigate the effect of midazolam on binding of mu-, delta- and kappa-ligands to rat spinal opioid receptors in the presence of sodium ions which differentially modulate binding of opioid agonists and antagonists. Sodium ions (50-1,000 mmol/l) selectively increased the specific binding of [3H]naloxone but decreased binding of opioid agonists such as [3H]DAGO (Tyr-D-Ala-Gly-Methyl-Phe-Gly-ol-enkephalin) to mu-receptors, [3H]DSTLE (Tyr-D-Ser-Gly-Phe-Leu-Thr-enkephalin) to delta-receptors and [3H]EKC (ethylketocyclazocine) to kappa-receptors in rat spinal cord in vitro. Midazolam (1-100 mumol/l) inhibited the binding of [3H]naloxone, [3H]DAGO, [3H]DSTLE and [3H]EKC. Sodium ions (100 mmol/l) antagonized the inhibition of binding of [3H]naloxone and [3H]DSTLE by midazolam by increasing IC50 values for midazolam. However, sodium ions potentiated the inhibition of binding of [3H]DAGO by midazolam by decreasing IC50 value for midazolam and had a mixed effect on binding of [3H]EKC in the presence of midazolam. Scatchard analysis performed in the presence of sodium ions and/or midazolam confirmed the specific effects of sodium ions as well as midazolam on the Bmax and KD of mu-, delta-, and kappa-receptors. These results suggest for the first time that sodium ions play an important role in the modulation of spinal opioid receptors by benzodiazepines. Sodium ions potentiate the inhibition of DAGO binding but antagonize the inhibition of naloxone and DSTLE binding by midazolam in rat spinal cord.

      Pubmed     Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…